S.T.A.L.K.E.R.: Call of Pripyat takes PC gamers once again into the deadly area surrounding the Chernobyl nuclear reactor explosion of 1986. Cordoned off by the military, this highly contaminated "Zone" is scoured by treasure hunters known as s.t.a.l.k.e.r.s, who search the irradiated lands for unique artifacts. In the role of Agent Alexander Degtyarev, the player must go undercover as a S.T.A.L.K.E.R., investigating the mysterious disappearance of five military helicopters while standing against various S.T.A.L.K.E.R. groups.

Using the time-tested X-Ray graphic engine developed by GSC Game World, S.T.A.L.K.E.R.: Call of Pripyat skilfully combines first-person shooter action with role-playing elements in a realistic post-atomic world. The grim realities of this deadly environment are underscored by the many desolate industrial ruins, reproduced using aerial pictures and the developers' own photographs. Mutants, S.T.A.L.K.E.R. groups, and lethal anomalies are everywhere, posing a constant threat to the player. The thrilling story is advanced through numerous quests, taking gamers through such diverse areas as a secret military base, the Jupiter factory site, and the titular city of Pripyat. The player decides how far to explore and which tasks they undertake – freedom determines the gameplay. Other S.T.A.L.K.E.R. groups respond to the player in a friendly or hostile manner, depending on the group to which they belong. In this ever-dangerous world, the player is supported by various weapon systems and upgrades, as well as several types of equipment.